Respiratory Infections

Study Outline on page 678-679

  1. Anatomy of the Respiratory Tree ( Upper Respiratory Tree).  Refer to the picture

q       Nasal Cavity

q       Oral Cavity

q       Tongue

q       Epiglottis

q       Trachea

q       Larynx

q       Tonsils

q       Eustachian Tube

 

Overview

Anatomy of respiratory system, adult

 

Sinuses and Nose

 

 

Respiratory Tree

Trachea

 

 

Alveoli

 

 

 

 

 

 

Microbial Diseases of the  Respiratory Tract( and descriptions of the pathogens )

 

q       Pharyngitis –Inflammation of the mucous membranes of the throat or sore throat

 

q       Laryngitis – Streptococcus pyogenes or Streptococcus pneumoniae  causes swelling of the vocal cords- there is an inability to speak

 

q       Tonsilitis – Inflammation of the tonsils – swelling in the throat – fever -

 

q       Sinusitis – nasal sinuses have mucous membranes that become infected with a variety of microorganisms .  There is a heavy discharge of mucous.  The sinuses can become blocked.  The blockage can cause pressure and pain.  These diseases may be self limiting – which means that the immune system overwhelms the infectious agent.

 

q       Epiglottitis – the epiglottis is a flap like cartilaginous structure that separates the respiratory tree from the digestive tract.  It is often infected by opprotunitstic organisms.  The vaccination for H. infleunze type b ( the Hib vaccine) has significantly reduced the occurrence of epiglottitis in the population.

 

Streptococcal Pharyngitis

q       Strep throat – Group A, Beta hemolytic strep.   This group is essentially only Streptococcus pyogenes.  This bacteria is responsible for many infections of skin and soft tissues.

q       Beta hemolytic streptococcus has been linked to impetigos well as endocarditis

                  ( inflammation of the lining of the heart)

q       Group A Beta hemolytic strep is resistant to the immune system and phagocytosis by the white blood cells.  The bacteria are able to produce special enzymes called streptokinases that lyse fibrin clots and streptolysins that are toxic to tissue cells, red blood cells, and protective leukocytes.

Why is Streptococcus pyogenes pathogenic

q       Capsule – The capsule is composed of hyaluronic acid.  The presence of this capsule fools the immune system because the hyaluronic acid outer covering is identical to human hyaluronic acid

q       Fimbriae – the fimbriae contain the virulence factor the M PROTEIN  The M proteins are antigenic and result in the formation of antibodies against this protein.  However, the M proteins are variable from strep to strep so it is possible that individuals become infected by different strep due to this factor.

q       Steptococcus releases exotoxins

q       Streptococcus releases cytolytic toxins and exoenzymes.

Streptolysin O is a hemolysin that causes damage to human white blood cells

It is strongly antigenic.

This antigen can be used to test for recent infection by an ASO test

 

Hyaluronidase – hydrolyzes the basic structure in human connective tissue

 

Streptokinase- catalyzes the conversion of plaminogen to plasmin- this results in the lysis of clots which hastens the spread of infection

q       Originally the presence of Group A Beta strep was verified by the culture of these organisms on 5% sheep blood agar.  The presence of beta hemolysis indicated Steptococcus pyogenes or strep throat.  Rapid strep tests have replaced the culture.  The culture could take 24 to 48 hours to identify the bacterium.  Now an agglutination diagnostic test is used to identify streprococcus.

Latex particles coated with antibodies against group A streptococci + streptococcus antigens yields a positive agglutination test.

q       There are individuals that are carriers for Beta streptococci

q       There are other causes of throat infections – viruses

q       Positive throat cultures are characterized by the inflammation of the throat and a fever.

q       The lymph nodes in the neck and throat are enlarged and tender.

q       This bacteria may also be accompanied by otitis media

q       There are 80 serological types of streptococcus- that are linked to a variety of diseases.

q       The most common mode of transmission for strep throat is by respiratory secretions

Scarlet Fever

q       When S pyogenes causes a sore throat and produces an erythrogenic ( reddening toxin) the resulting infection is called scarlet fever.

q       When the bacteria produces this toxin it has been lysogenized by a bacteriophage.

Refer to the picture.  Lysogeny is an interaction between a bacteriophage

( bacterial virus) and a bacteria

 

q       The toxin causes a skin rash with is due to a hypersensitivity to the toxin.  The tongue has a spotted, strawberry like appearance and then, as it loses its upper membrane.

a.The skin can peel off

b.It is severely uncomfortable to eat

c.   It is highly infectious

Additional pathogenesis of strep in other organ systems

Impetigo

q       Childhood disease

q       Usually begins on the legs

q       It can severe and extensive lesions on the face and limbs

q       Impetigo is treated with a topical agent such as mupirocin ro systemically with penicillin.

 

GAS

q       Invasive group A streptococcal ( GAS) disease

 Common during the first half of the century it has recently reemerged to become a problem. 

q       Patients have a deep local invasion without necrosis – this has been referred to as

 “ Flesh eating bacteria”    It can lead to bacteremia and sepsis

Symptoms may include fever, hypotension, and multi-organ involvement

Streptococcus pneumonia

q       Gram positive, nonmotilve encapsulated cocci.  Their shape is described as lancet shaped.  Their tendency to occur in pairs led to their identification as diplococcus pneumonia. 

q       This is the most common cause of bacterial pneumonia and otitis media

The risk of this disease is highest in babies, children, the elderly, and smokers.

 Streptococcus pneumonia causes alpha hemolysis in blood cultures

The capsule is antiphagocytic and antigenic.  The bacteria are protected from the attacks of neutrophils

 

segmented neutrophil

The capsules are antigenic – however there are 85 distinctive types o capsules .  Some of these capsules are more antigenic than others.

The occurrence of pneumonia is related to the increased level of secretions that are difficult to clear from respiratory passageways as well as by secondary infections of viruses.

q       Otitis media is most frequently caused by pneumococcus as a primary infection and then can be followed by Haemophilus influenzae.  The traditional treatment for this bacterium is a beta lactam antibiotic- one that inhibits the growth of the cell wall   

Diptheria

q       Upper respiratory tract infection.  It used to be a killer.

q       Diptheria is caused by Cornybacterium diptheriae, a gram positive non- endospore forming rod.  It is pleomorphic which means that its shape is variable.  It has been described as a club shaped bacterium.

q       This infections begins with a sore throat and swollen lymph nodes

q       The diptheria toxoid  is the component of the DPT vaccine that causes the body to produce antibodies against the diptheria toxi

q       C. diptheriae has adapted to an immunized population.  Many people today carry non pathogenic strain of bacteria

q       The characteristics of diptheria are to produce a membranous structure in the airways that can block respiration.  This membrane that blocks the upper airways is formed by a fibrin like clot, bacterial cells, and white blood cells  

q       These bacteria can also produce an exotoxin when they are infected by a bacteriophage.

q       If the toxin circulates in the blood stream it can enter tissue cells and affect organs such as the heart and kidneys.  If the toxin affects the nerves paralysis can occur

q       Laboratory analysis requires both selective and differential media

q       Penicillin and erythromycin are used to treat the bacterial infection

Mortality

  1. The death rate for respiratory cases is still from 5-10%.
  2. Previously immunity was maintained in the population by inoculations
  3. Immune levels are now probably lower than 20%

Cutaneous diptheria

  The Common Cold

Rhinoviruses

 

http://www.niaid.nih.gov/factsheets/cold.htm _ NAID

a.  About 50% of colds are caused by a group of viruses called rhinoviruses

b.  Corona viruses cause many other types of infections

c.  Sneezing, secretions, congestion

d.  Infections can spread to the sinuses or to the lower respiratory tract causing complications.

e.  Rhinoviruses are highly infectious.  It may not cause the presence of many viral particles to initiate the disease process.

f.  There is no therapy( antibiotic) because colds are caused by viruses.  It takes about a week for recovery.

 

Pertussis - Whooping Cough

 

 

a.  Small obligate aerobic gram negative coccobacillus

b.  The virulent or pathogenic strains have an outer capsule.

c.  The bacteria attach to the psuedostratified epithelial cells in the respiratory tree that have cilia

d.  The attachment of the bacterial cells to the cilia impedes their sweeping motion which tens to clear bacteria from the respiratory tree.

e.  Tracheal cytotoxin- bacterial cytotoxin that destroys the cells lining the respiratory tract

f.  The pertussis toxin can enter the blood stream and produce systemic effects

Stages

Catarrhal- common cold

Paroxysmal- coughing - the accumulation of mucous caused by the destruction of the ciliated cells, makes breathing difficult.  The whooping sound is the result of gasping for air between coughs

Vaccinations

Lowered the incidence of this disease in the United Stats. In the 1950's the number of cases numbered 250,000.  Today there are as many as several thousand, but very few deaths.

Vaccinations are acellular - which refers to the fact that the vaccine contains antigens from the bacterium rather than an attenuated strain

Tuberculosis

 

Tuberculosis Genome

a.  Tubercuolosis is an infectious disease caused by Mycobacterium tuberculosis

b.  The rods are slow growing and grow in clumps

c.  They almost appear mold like in the media

d.  These bacteria do not stain well with the Gram Stain .  An Acid Fast Stain using a carbol fuschin dye cannot be decolorized with acid-alcohol and can be classified as acid-fast

e.  The unusual nature of the cell wall which contains extra lipids provides extra resistance to dehydration or drying

 

TB

a.  May be fought by natural immune defenses

Fluorescent micrographs of macrophages and TB bacterium

b.  Individuals are more susceptible if they are exposed to additional pathogens, malnutrition, environmental stresses( air pollution)

c.  Usually acquired by inhalation of the bacterium - that is the mode of entry for the bacterium into the body

Tuberculosis and The Immune System   

a.  Tuberculosis reaching the alveoli of the lungs are ingested by macrophages

b.  The bacteria multiply inside of the macrophages- This initiates a chemotactic response that attracts other immune cells.  The release of cytokines by macrophages are not necessarily successful at killing the tuberculosis and can in fact cause lung damage.

Tuberculosis in the lung

c.  The macrophages may die and form a tubercle.  Inside the tubercle there may be bacteria that are capable of initiating a new infection after a period of dormancy.

d.  The type of immune response is therefore cell mediated because the TB bacteria are actually within the macrophages.

TB TEST

a.  A purified protein extract from the bacterium is inoculated cutaneously

b.  If the person receiving the inoculation has been infected in the past - T cells will initiate a response- it is considered to be a hypersensitivity reaction and the skin becomes red and the site of inoculation swollen

c.  A positive TB test in someone young is probably indicative of an active case

d.  In older individuals the positive test may indicate a previous vaccination or infection.  In this case the positive reaction will be followed up X- Rays

Pulmonary nodule - front view chest X-ray 

TB nodules in X-ray

BCG Vaccine

a.  Live culture of Mycobacterium bovis, which has been made by attenuation- made avirulent by repeated passages through media

b.  The vaccine is used for children in high risk situations and environments.

c.  About 20,000 cases of tuberculosis are reported yearly.  The mortality rate is decreasing.

d.  One of the larges problems is the occurrence of TB in immigrants from Asia, the Philippines, and Mexico

 

Mycoplasma pneumoniae-

a.  These bacteria do not have cells walls made of peptidoglycans

b.  These may be confused with viral pneumonia

c.  Found in individuals with weakened or compromised immune system

d.  This is an atypical infection which responds to tetracylines

e.  Primary atypical walking pneumonia

f. Sputum specimens are cultured.  When they are grown on enriched media containing both yeast and horse serum, they produce colonies that have a " fried egg" appearance.

g.  The colonies are quite small and the bacterium slow growing so that as long as two weeks may be required for the colonies to grow.  It is therefore imperative to use more sophisticated means of diagnosis such as PCR which can yield results within hours.

 

Legionnaries's Disease

 

a.  Received attention in 1976 at a meeting of the American Legion which was held in Philadelphia, Pennsylvania.

b.  The symptoms of this infection by a rickettsial organismms, Legionella pneumophila,cause symptoms of extremely high fever and cough.  

c.  MOrphologically it is a gram - bacterium that can be traced to air conditioner ducts, humidifiers, and showers.

d.  They are highly resistant to chlorine and heat

e.  The diagnosis is made by culture on a charcoal-yeast media

 

Psittacosis( Ornithosis)

a.  Is a term that describes the source of infection from parakeets and parrots

b.  This disease may also be contracted from chickens, pigeons, and other birds

c.  The symptoms of this disease include fever, high fever, headache and chills

d.  The common mode of infection is from the dried particles from bird droppings

e.  Tetracyclines are effective antibiotics in treating both animals and man. 

 

Influenza Virus

a. Infects many individuals each year

b.  characterized by fever, headache, and muscular aches

c.  10,000-20,000 individuals die yearly from this virus

 

a.  Consists of eight separate RNA segments( RNA virus with a segmented genome)

b. Inner layer or protein covered by a lipid envelope( enveloped virus)

c.  Two types of spikes on the exterior

hemagglutinin - _ H spikes are used for cellular recognition and infection

neuraminidase - N spikes allow the virus to exit the infected cell after it reproduces

Antigenic shifts - mutations or differences in the H or N spikes

Antigenic drifts- minor changes in the viral spikes

Histoplasmosis capsulatum - Fungal Respiratory Disease

 

 Fungal infection of the respiratory tract.  It has stages in which it resembles yeast and stages in which it resembles mold.

Humans acquire the spores if the conditions are correct( humidity) as well as the pH.

These conditions occur where there are high concentrations of bat and bird droppings  Bats have a lower body temperature than birds, carry the fungus, excrete it in their feces, and infect soil

 

 

OHIO and Mississippi River Valleys

Coccidioidomycosis

Another fungal infection that can be found in the American Southwest

Spores are carried by the air( arthrospores).  They are inhaled and the infection ensues

Very high incidence in California and Arizona - environmental disturbances exacerbate the level of infection in these areas

Amphotericin B and Imidazole drugs are used to treat this disease

 

Peumocystis pneumonia

Fungi or protozoan

Attacks immunosuppressed patients( HIV patients )

The microbes inhabit the lining of the aqlveoli

They form a thick-walled cysts